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The antitumor activity of resveratrol, a polyphenolic compound found mainly in grapes, has been studied in several types of cancer. In bladder cancer, its antiproliferative effects have already been demonstrated, however its mechanism of action is not completely understood. The aim of this study was to evaluate resveratrol antitumor activity (12.5, 25, 50, 100, 150, 200 and 250 μM) and its possible mechanisms of action in bladder tumor cells with different TP53 gene status (RT4, grade 1, TP53 wild type; 5637-grade 2 and T24-grade 3, TP53 mutated). Cell proliferation, clonogenic survival, morphological changes, cell cycle progression, apoptosis rates, genotoxicity, global methylation, immunocytochemistry for p53 and PCNA and relative expression profiles of the AKT, mTOR, RASSF1A, HOXB3, SRC, PLK1 and DNMT1 were evaluated. Resveratrol decreased cell proliferation and induced DNA damage in all cell lines. Regarding the long-term effects, resveratrol reduced the number of colonies in all cell lines; however, TP53 wild type cells were more resistant. Increased rates of apoptosis were found in the TP53 wild type cells and this was accompanied by AKT, mTOR and SRC downregulation. In addition, the resveratrol antiproliferative effects in wild type TP53 cells were accompanied by modulation of the DNMT1 gene. In the TP53 mutated cells, cell cycle arrest at S phase with PLK1 downregulation was observed. Additionally, there was modulation of the HOXB3/RASSF1A pathway and nuclear PCNA reduction in the highest-grade cells. In conclusion, resveratrol has antiproliferative activity in bladder tumor cells; however the mechanisms of action are dependent on TP53 status. This article is protected by copyright. All rights reserved.
This article was published in the following journal.
Name: Environmental and molecular mutagenesis
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Tumors or cancer of the URINARY BLADDER.
A HERNIA-like condition in which the weakened pelvic muscles cause the URINARY BLADDER to drop from its normal position. Fallen urinary bladder is more common in females with the bladder dropping into the VAGINA and less common in males with the bladder dropping into the SCROTUM.
Involuntary discharge of URINE as a result of physical activities that increase abdominal pressure on the URINARY BLADDER without detrusor contraction or overdistended bladder. The subtypes are classified by the degree of leakage, descent and opening of the bladder neck and URETHRA without bladder contraction, and sphincter deficiency.
Tumor-selective, replication competent VIRUSES that have antineoplastic effects. This is achieved by producing cytotoxicity-enhancing proteins and/or eliciting an antitumor immune response. They are genetically engineered so that they can replicate in CANCER cells but not in normal cells, and are used in ONCOLYTIC VIROTHERAPY.
C-type lectins that restrict growth of bacteria in the intestinal epithelia and have bactericidal activity against gram-positive and gram-negative bacteria. They also regulate proliferation and differentiation of KERATINOCYTES following injury. Human pancreatitis-associated protein-1 (Reg3a) is overexpressed by pancreatic ACINAR CELLS in patients with CHRONIC PANCREATITIS. It is also highly expressed by pancreatic, bladder, and gastrointestinal cancer cells and may serve as a diagnostic biomarker.
Non-invasive bladder cancer is a cancer that is only in the inner lining of the bladder. Invasive bladder cancer is cancer that has spread into the deeper walls of the bladder. When the cancer has spread outside the bladder to other parts of the body, th...
Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...